Type 1 diabetes genetic risk score discriminates between monogenic and Type 1 diabetes in children diagnosed at the age of <5 years in the Iranian population.

AIM: To examine the extent to which discriminatory testing using antibodies and Type 1 diabetes genetic risk score, validated in European populations, is applicable in a non-European population. METHODS: We recruited 127 unrelated children with diabetes diagnosed between 9 months and 5 years from two centres in Iran. All children underwent targeted next-generation sequencing of 35 monogenic diabetes genes. We measured three islet autoantibodies (islet antigen 2, glutamic acid decarboxylase and zinc transporter 8) and generated a Type 1 diabetes genetic risk score in all children. RESULTS: We identified six children with monogenic diabetes, including four novel mutations: homozygous mutations in WFS1 (n=3), SLC19A2 and SLC29A3, and a heterozygous mutation in GCK. All clinical features were similar in children with monogenic diabetes (n=6) and in the rest of the cohort (n=121). The Type 1 diabetes genetic risk score discriminated children with monogenic from Type 1 diabetes [area under the receiver-operating characteristic curve 0.90 (95% CI 0.83-0.97)]. All children with monogenic diabetes were autoantibody-negative. In children with no mutation, 59 were positive to glutamic acid decarboxylase, 39 to islet antigen 2 and 31 to zinc transporter 8. Measuring zinc transporter 8 increased the number of autoantibody-positive individuals by eight. CONCLUSIONS: The present study provides the first evidence that Type 1 diabetes genetic risk score can be used to distinguish monogenic from Type 1 diabetes in an Iranian population with a large number of consanguineous unions. This test can be used to identify children with a higher probability of having monogenic diabetes who could then undergo genetic testing. Identification of these individuals would reduce the cost of treatment and improve the management of their clinical course.

Association of body mass index and Trp64Arg polymorphism of the beta3-adrenoreceptor gene and leptin level in Tehran Lipid and Glucose Study.

In this study the association between beta3-adrenoceptor gene polymorphism and serum concentration of leptin with body mass index (BMI) is investigated. Using subjects in the Tehran Lipid and Glucose Study, genotyping of the Trp64Arg polymorphism of the beta3-adrenoreceptor gene was performed using a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique was used and the association with obesity was investigated. At total of 197 men and 204 women were divided into four groups (BMI<20, 20< or =BMI<25, 25< or =BMI<30, BMI< or =30) and 97, 98, 104 and 102 subjects, respectively, were placed randomly in the four groups. Leptin level was determined by an enzyme immunoassay (EIA) method and FBS, HDL-C, triglyceride and total cholesterol levels were determined by an enzyme colorimetric method. Body mass index (BMI) was also measured. The A (Arg) allele frequency was 0.08 among the population and its presence was significantly associated with increase of leptin level (AA/TA, 30.5+/-24.8 ng/mL; TT, 22.6+/-20.9 ng/mL; P=0.014) but there was no significant association with increased BMI (AA/TA, 27+/-5.6 kg/m2; TT, 25.4+/-5.5 kg/m2; P=0.072). These data show that the presence of the Arg64 allele at the beta3-adenoceptor gene locus is related to increase in leptin level in this population, but is not related to body mass index.

Measurement of radioactivity in Arizona groundwater using improved analytical techniques for samples with high dissolved solids.

Radiochemical analyses of 667 samples collected over the 5-y period 1989 to 1993 indicate that approximately 2% of Arizona drinking water supplies from groundwater sources violate current regulatory standards. About 1% of the population is affected. The 1996 change in regulatory requirements will bring some Arizona water systems into compliance through 226Ra limit relaxation, while others will become noncompliant due to new limits on uranium levels. Maximum concentrations in Arizona of adjusted gross alpha, gross beta, and 226Ra activities are higher than levels found in the U.S. Environmental Protection Agency's national survey. Sampling results show a correlation between radionuclide concentration and localized geology. Improved radiochemical methods are described that result in greater accuracy and sensitivity for samples high in dissolved solids, as are typical in Arizona.